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3/4 new here with high LDL after 3-months keto

Newcomer introductions, personal anecdotes, caregiver issues, lab results, and n=1 experimentation.
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apoe4thebetter
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3/4 new here with high LDL after 3-months keto

Postby apoe4thebetter » Sun Jun 28, 2020 7:46 pm

Hello, I’m an apoE3/4 new to the forum, and I’ve really gotten a big boost out of all the great info here—thank you to Dr. Stavia for the primer and to all the contributors for sharing!

Here’s my story: I’ve known I have a copy of the apoE4 allele for more than a year now, but I’ve been more concerned with type-2 diabetes risk since both parents have adult-onset T2D and my A1c was creeping up. They are in their 80s and 90s with otherwise good health for their ages, so AD was for me hopefully of secondary concern from a family history perspective (we don’t know their apoE classifications). I’m a lean, fit 56-year old male and have been working to get off the standard American diet. First, I eliminated sugar and simple carbs, and that worked for a couple years. But the A1c crept up again.

Three months ago, I started a keto experiment. I had been wanting to try going keto to improve my fat adaptation, partly for the metabolic benefits and partly for endurance performance as a runner. Shelter-in-place gave me that opportunity since I was home and cooking every day. After the transition to keto I feel great physically and mentally, love the food choices and don’t miss the carbs at all, and was looking forward to seeing how my labs look. A1c was lower—down to 5.2 (yay!), and everything else looked great except LDL was high—LDL-C went from pre-keto 109 (above optimal) to 173 (high). To get a better picture, I did my first NMR profile. LDL-P was 2042 (very high), and small LDL-P was 577 (high) although LDL particle size was 21.4 which I understand indicates the more favorable pattern A (fluffy). HDL and TG both went up a bit from pre-keto and are good (49->67 and 53->58, respectively). LP-IR is <25 (yay!). I water-only fasted for 13 hours before the blood draw.

In the keto/low-carb community, many don’t seem to be concerned about high LDL, but I didn’t want to dismiss it so quickly, so I’ve been digging into how I could bring the LDL back down but still stay keto. That brought me to your site and others where I learned my apoE4 copy not only increases my AD risk but could also be affecting my lipids particularly on a diet with high amounts of saturated fat. Like many who start keto, I replaced a large part of the calories I used to get from carbs with coconut (which I found I like) including MCT oil which is 100% saturated fat.

I realize from reading here and elsewhere that the science in this space requires a lot of n=1 experimentation to find out what works best for me, and I’m encouraged reading about those here and elsewhere who have seen LDL come down from high levels when reducing SFA in their diets. I’m now a couple of days into an experiment where I have replaced SFAs with MUFAs as much as possible. For example, I’ve cut all coconut and replaced it with EVOO and macadamia nuts, was already eating a whole avocado almost every day, and stopped putting butter in my coffee (always pre-keto loved it black). Basically I’m working to drive the SFAs down as close to back to where they were pre-keto hoping to reduce the LDL back to where it was pre-keto, although I realize EVOO and macadamia nuts while mostly MUFAs do contain some SFAs and PUFAs.

Now that I’ve achieved some level of fat adaptation (I can do a longer run without carbs and feel great), I’m also adding to the MUFA experiment a cycle of one day per week with low fat and healthy carb refeeding. My goal is metabolic flexibility ie. giving my body the option to use glycogen and fat stores for longer runs or heavier workouts. Cyclic keto appeals to me as being more ancestral, and I’ve now got some headroom with my A1c to add back a few healthy carbs like (sweet potatoes, oats, LGI fruits, etc.). It will be interesting to see what if anything a cyclic carb refeeding day per week does for LDL.

Going back 20+ years ago when I was less physically active, I had a history of low HDL-C (25). Back then to address that I started supplementing high-dose immediate-release niacin, pantethine, and phytosterols. I continued that supplementation with favorable results until 2016 when my doctor said I could probably drop the niacin supplements because I was much more physically active (running, swimming, weightlifting, etc.). My last TC/TG/HDL/LDL numbers on niacin in 2016 were 156/59/56/88. She was right--dropping the niacin yielded 171/41/54/109, so HDL stayed in the mid-50s, TG was down, and TC and LDL were up but not enough for great concern.

I continued supplementing the pantethine and phytosterols, but after reading in the wiki “Supplementing with plant sterols to reduce total cholesterol and LDL cholesterol doesn't work for E4 carriers”, I’m now dropping the phytosterols as part of the current MUFA cyclic keto experiment. Good to know after 20 years I never needed them! I found a few references on this site to those supplementing pantetheine, so I’ll continue it. Also, I would consider perhaps a later experiment with adding back the immediate-release niacin supplements since four years ago that seemed to give me a 20-point drop in LDL-C, and my numbers since dropping niacin have never been as good. But I see niacin seems to have lost favor over the years, and I’m not sure if the effect is the same on keto. I’m hoping the shift from SFAs to MUFAs will be sufficient (fingers crossed).

I'm glad I found this site and excited to be a new member. Based on all the positive feedback I have ordered Dale Bredesen’s “The End of Alzheimer’s”. I will also continue to dig into all the great info here for further insights and again appreciate all the sharing.
apoe4thebetter | 3/4 | currently doing keto experiments to work through A1c and LDL challenges

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Re: 3/4 new here with high LDL after 3-months keto

Postby MarcR » Sun Jun 28, 2020 8:27 pm

Great handle and first post, apoe4thebetter - welcome. You seem to have a solid strategy and are refining and optimizing rather than fixing big problems - congratulations on being so well-positioned for an extended health span.

I imagine that you are familiar with Dave Feldman's work, but just in case you haven't come across it, I recommend his Cholesterol Code blog and his Lean Mass Hyper Responder Facebook group.

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Re: 3/4 new here with high LDL after 3-months keto

Postby MicheleCC » Sun Jun 28, 2020 9:58 pm

apoe4thebetter wrote:Hello, I’m an apoE3/4 new to the forum, and I’ve really gotten a big boost out of all the great info here—thank you to Dr. Stavia for the primer and to all the contributors for sharing!

Here’s my story: I’ve known I have a copy of the apoE4 allele for more than a year now...
I'm glad I found this site and excited to be a new member. Based on all the positive feedback I have ordered Dale Bredesen’s “The End of Alzheimer’s”. I will also continue to dig into all the great info here for further insights and again appreciate all the sharing.


Welcome apoe4thebetter! Wow! It's inspiring to see someone so curious and motivated to understand their genetics and physiological functioning! You've done an amazing job of tracking your biomarkers and learning what works and doesn't work for you AND THAT is a key to health--know thyself! It's great to hear that you've found valuable information on this site and are learning from other site users. I'm eager to hear more about how the current changes you're making influence your lipid biomarkers.

As an intern on this site, it is my official role to welcome you and to point you to some aspects of the site that may be helpful. You've already found the Primer by Stavia--an excellent place to start learning about apoe4. You've shared your story and clearly have done your research on the site. So, it sounds like you have a great grasp on using forums and searching wikis. Do you have any questions about the site? There are many very well educated and informed users and contributors here, and now you are one of them! Thank you for a great first post and sharing your story. I'm confident others here will benefit and learn from it.

If you have any questions or there's something you haven't been able to figure out about the site, please respond to this post by clicking on the quotation marks to the right of the post title--that will alert me that you have a question. I hope your experiment with diet and supplements continues to give you the desirable results!

Warm regards,
MicheleCC
Functional Medicine Certified Health Coach
Certified Nutrition Educator & Consultant
Board Certified in Holistic Nutrition (NANP)

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Re: 3/4 new here with high LDL after 3-months keto

Postby SusanJ » Mon Jun 29, 2020 8:16 am

apoe4thebetter wrote:Here’s my story: I’ve known I have a copy of the apoE4 allele for more than a year now, but I’ve been more concerned with type-2 diabetes risk since both parents have adult-onset T2D and my A1c was creeping up.


Welcome! As a sister 3/4, whose father had T2D, I hear the struggle. Dropping coconut oil will definitely help, but my experience is the good carb/fat dance is a tight one when it comes to balancing A1c and LDL. One other thing to consider, is that my current doctor (treats Alzheimer's patients, works with Bredesen and took me on as one of his prevention patients) is working on cutting my inflammatory burden (metals and viruses). He sees that fixing inflammation causes LDL to drop, so if you can't get where you want to be with lipids, look for any inflammation that might be happening.

Good luck and let us know how your experiments go!

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Re: 3/4 new here with high LDL after 3-months keto

Postby apoe4thebetter » Mon Jun 29, 2020 9:08 am

MarcR wrote:Great handle and first post, apoe4thebetter - welcome. You seem to have a solid strategy and are refining and optimizing rather than fixing big problems - congratulations on being so well-positioned for an extended health span.

I imagine that you are familiar with Dave Feldman's work, but just in case you haven't come across it, I recommend his Cholesterol Code blog and his Lean Mass Hyper Responder Facebook group.


Thanks, MarcR! I did find Dave Feldman's work and found it very interesting, but I'm not comfortable with my very high LDL-P quite yet. In my digging I found Peter Attia had Dave on his podcast for a long, very interesting discussion, and right now I agree with Peter that Dave has some holes to fill. I will continue to follow his work.
apoe4thebetter | 3/4 | currently doing keto experiments to work through A1c and LDL challenges

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Re: 3/4 new here with high LDL after 3-months keto

Postby apoe4thebetter » Mon Jun 29, 2020 9:20 am

SusanJ wrote:
apoe4thebetter wrote:Here’s my story: I’ve known I have a copy of the apoE4 allele for more than a year now, but I’ve been more concerned with type-2 diabetes risk since both parents have adult-onset T2D and my A1c was creeping up.


Welcome! As a sister 3/4, whose father had T2D, I hear the struggle. Dropping coconut oil will definitely help, but my experience is the good carb/fat dance is a tight one when it comes to balancing A1c and LDL. One other thing to consider, is that my current doctor (treats Alzheimer's patients, works with Bredesen and took me on as one of his prevention patients) is working on cutting my inflammatory burden (metals and viruses). He sees that fixing inflammation causes LDL to drop, so if you can't get where you want to be with lipids, look for any inflammation that might be happening.

Good luck and let us know how your experiments go!


Thank you, Susan! Reducing inflammation was another reason I wanted to get fat adapted since fat and ketones are supposed to burn cleaner than glucose. I did have a CRP test done last year, and it came back low, but I see there are lots of inflammatory markers. I just ordered Bredesen's book, and it is supposed to arrive today. I'm glad to hear you've found a great doctor to address the metals and viruses--they are hard to find.
apoe4thebetter | 3/4 | currently doing keto experiments to work through A1c and LDL challenges

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Re: 3/4 new here with high LDL after 3-months keto

Postby SusanJ » Mon Jun 29, 2020 10:07 am

apoe4thebetter wrote:I did have a CRP test done last year, and it came back low, but I see there are lots of inflammatory markers.


All of my "typical" inflammatory markers have been low, CRP, TNF-alpha, fasting insulin, except for A1c. But my TGF-beta test last summer was really high, so that's when we focused on heavy metals (my arsenic was high, just did a blood draw so we'll see) and viruses. When you get the book, maybe take a longer look at the section on the inflammatory AD type, but also consider type 3, where other things like Lyme or mold can be problematic.

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Re: 3/4 new here with high LDL after 3-months keto

Postby apoe4thebetter » Mon Jun 29, 2020 11:54 am

MicheleCC wrote:
apoe4thebetter wrote:Hello, I’m an apoE3/4 new to the forum, and I’ve really gotten a big boost out of all the great info here—thank you to Dr. Stavia for the primer and to all the contributors for sharing!

Here’s my story: I’ve known I have a copy of the apoE4 allele for more than a year now...
I'm glad I found this site and excited to be a new member. Based on all the positive feedback I have ordered Dale Bredesen’s “The End of Alzheimer’s”. I will also continue to dig into all the great info here for further insights and again appreciate all the sharing.


Welcome apoe4thebetter! ....
Warm regards,
MicheleCC


Thanks for the warm welcome, MicheleCC! I think it's great that you're interning here, and I'll let you know if I have any questions.
apoe4thebetter | 3/4 | currently doing keto experiments to work through A1c and LDL challenges

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Re: 3/4 new here with high LDL after 3-months keto

Postby apoe4thebetter » Mon Jun 29, 2020 12:14 pm

SusanJ wrote:
apoe4thebetter wrote:I did have a CRP test done last year, and it came back low, but I see there are lots of inflammatory markers.


All of my "typical" inflammatory markers have been low, CRP, TNF-alpha, fasting insulin, except for A1c. But my TGF-beta test last summer was really high, so that's when we focused on heavy metals (my arsenic was high, just did a blood draw so we'll see) and viruses. When you get the book, maybe take a longer look at the section on the inflammatory AD type, but also consider type 3, where other things like Lyme or mold can be problematic.


Good to know, Susan. Thank you. Hope you get great results from the recent blood draw!
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Re: 3/4 new here with high LDL after 3-months keto

Postby apoe4thebetter » Wed Oct 21, 2020 11:44 pm

It been a while and wanted to provide an update on my n=1 experimentation since I have had some favorable results in terms of bringing down my LDL-P. I'm now following a diet that I’ve morphed into cyclic keto with some supplements and time-restricted eating. Let me first say that this experimentation is based on medical advice I’ve gotten previously from my doctor along with new ideas I got through research that I’ve done here on the forum and elsewhere. I have my annual checkup on Nov 3 with a new doctor (my previous doctor moved on) to make sure I’m not missing something.

Since I did my first NMR on June 16 that came back with LDL-P >2000 (very high), here’s a quick summary of the two experimental periods over 16-weeks. The values are from NMR tests through Labcorp after 12 hours of fasting, and I’ve listed the results in this order: TC/TG/HDL-C/LDL-C/LDL-P/Small LDL-P/LDL Size/HDL-P.

June 16: 252/58/67/173/2042/577/21.4/32.9

July 27: 214/46/59/146/1699/269/21.3/28.7

Oct 5: 169/46/58/101/1144/255/21.0/29.5

My focus has been on reducing LDL-P, and in 16 weeks I’ve been able to bring it down from 2042 (very high) to 1144 (moderate). Small LDL-P is also down from 577 to 255 (<527 preferred). I don’t have NMR data before June 16, but my Oct 21, 2019, conventional cholesterol results when my blood glucose had crept into pre-diabetic ranges were 169/53/49/109 (TC/TG/HDL-C/LDL-C), so those cholesterol results are now back to pretty close to that while I'm now much more metabolically healthy (fasting glucose down from 101 to 92 and A1c from 5.8 to 5.2).

Here’s the two experiments over a 16-week period:

For 6 weeks between June 16 and July 27, my first n=1 experiment was changing what I ate, and that yielded a nice 15% reduction in LDL-P from 2042 (very high) to 1699 (high), and it dropped small LDL-P in half. Here’s a run-down:
• Replaced SFA with MUFA: I eliminated coconut (coconut oil, coconut butter, MCT, etc.) and reduced dairy but kept the grass-fed beef, and I added more EVOO, macadamia nuts, and avocados
• Shifted from strict keto to cyclic keto: I added a carb refeed day to every week. Since I was feeling good about my progress to fat adaptation, I bought into the idea of refeeding with healthy carbs as being more ancestral and beneficial to adrenal health and intense exercise, so one day a week I reduce the healthy fats and add ~150 grams of carbs with sweet potatoes, beets, rice, oats, butternut squash, banana, and/or an apple, etc. My family and friends call it my “cheat day”, but I still decline wheat and simple carbs. I time the carb refeed with workouts with heavier weights and higher intensity training to take advantage of the replenished glycogen stores, and I usually increase protein on this day by 30g or so with whey isolate and/or pea protein. Then I time a longer run or longer fast for the day after to burn off the glycogen, and I’m usually pretty quickly back into nutritional ketosis.

Six weeks wasn’t that long, and it may have come down further just with these changes over time, but I still wasn’t comfortable with LDL-P that high. I’m aware of the hypothesis about hyper-responders with low TG and high HDL (Dave Feldman et al), but until that gets a bit more traction, I was determined to see what I could try to stay cyclic keto and bring LDL-P down further. My interest in keto is not just lower blood glucose, lower insulin, lower inflammation, etc. but also endurance performance ie. being fat-adapted to do longer runs without being dependent on carbs.

So, during the 10 weeks between July 27 and October 5, my next experimentation was with adding supplements and timing when I was eating but keeping the cyclic keto diet as it was in the previous 6 weeks ie. with SFA replaced by MUFA. The good news is that these 10 weeks yielded a 33% improvement in LDP-P down from 1699 (high) to 1144 (moderate), but the unfortunate news is that I don’t know how much each of these changes contributed to the improvement. Here’s a run-down:
• Added daily 2x500mg Berberine: Based on what I’ve read here on the forum, from Bredesen, and elsewhere about Berberine’s positive effects on blood glucose and cholesterol, I decided to give it a try. I take it with a little MCT oil (I know it’s from coconut) on an empty stomach to improve bioavailability. It seems to be hit-or-miss with some people seeing a bigger benefit than others. I haven’t noticed any effect on my blood glucose (it’s already nicely controlled by my diet), and I wish I knew how much this might be contributing to the LDL-P change. This reference says “Berberine alone and in combination with other dietary supplements provides an average LDL percentage lowering capability of 20% to 30%.” (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871262/)
• Added daily 2x500mg immediate-release niacin: I was taking this dosage of IR niacin for 20+ years to increase HDL-C before I stopped it several years ago when I started exercising and found I didn’t need it for HDL any more. When I stopped it, my LDL-C increased ~20 points from ~90 to ~110, so I know that niacin was at that time having a non-trivial benefit on my LDL-C. I was reluctant to start it again given that it seems to have lost favor, but since there are still positive reports about it and since I knew I tolerated it well, I decided to resume it. The flushing side effect for me is relatively minor, and after these 10 weeks my liver enzymes are still normal (I recall it’s very important to check liver enzymes regularly on high dosages of niacin because of the burden on the liver, and I’ve never had problems with 2x500mg). I realize that LDL-C is not as meaningful as LDL-P, but during this 10 weeks LDL-C reduced from 146 to 101, so you could conclude that the resumption of niacin contributed perhaps 20 points to that 45-point reduction (almost half). At some point I might try reducing or stopping the niacin again to see how much it actually is contributing to the LDL-P improvement.
• Implemented more deliberate time-restricted eating: I had already started skipping breakfast with black coffee only until lunch, and then I discovered the Zerofasting app—it’s awesome at helping me put more discipline into time-restricted eating. I am now doing mostly 16:8 with some 20:4 days and even some 22:2 OMAD days—it’s so easy with the app! Looking forward to trying some prolonged fasts with it eventually.

A couple of other observations: The 6-week SFA->MUFA and cyclic keto experiment reduced TG and HDL-C about 20% and 10% respectively, and HDL-P dropped below 30.5 where it’s now flagged as low. The 10-week supplement experiment didn’t change TG or HDL-C at all although HDL-P improved a bit (still low). LDL size didn’t move much at all in either experiment which is good since it’s consistently been >20.5 which means the preferred pattern A (fluffy).

My next step is to run this by my new doctor at my annual checkup on Nov 3 to make sure I’m not missing something, and I’m pretty excited with the results so far and wanted to share in case my story helps someone here bring any of this up with their doctor. Thanks again to all who are posting here sharing your journey. Through your stories you are helping me with mine!
apoe4thebetter | 3/4 | currently doing keto experiments to work through A1c and LDL challenges


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